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Synthetic Phosphoantigens Enhance Human Vγ9Vδ2 T Lymphocytes Killing of Non-Hodgkin’s B Lymphoma

2001; BioMed Central; Volume: 7; Issue: 10 Linguagem: Inglês

10.1007/bf03401961

1528-3658

Hélène Sicard, Talal Al Saati, Georges Delsol, Jean‐Jacques Fournié,

RNA Interference and Gene Delivery

Non-Hodgkin's B lymphomas (NHL) are often resistant to conventional treatments and, until now, immunotherapeutic approaches against NHL only aimed at inducing αβ anti-tumor effectors. Nevertheless, human blood Vγ9Vδ2 T lymphocytes represent an abundant pool of cytotoxic tumor-reactive cells. Vγ9Vδ2 T cells are strongly activated by natural compounds, from which powerful synthetic ligands have been derived. These synthetic antigens induce efficient Vγ9Vδ2 T cell responses in vitro. We set up a series of Vγ9Vδ2 T cell-activation experiments, including cytotoxic activity and amplification from whole blood cells. Several types of Vγ9Vδ2 effectors were challenged against a panel of 16 B lymphoma cell lines. These tests have been performed in the absence and presence of γδ-specific synthetic ligands to evaluate the effect of such molecules on γδ anti-tumor activity. We report here that Vγ9Vδ2 T cells recognize B lymphomas. This recognition is associated with the cytotoxic activity against B-lymphoma cells and/or proliferative responses, and appears to be T-cell antigen receptor (TCR)-dependent. Because few B lymphoma induce a complete set of Vγ9Vδ2 cell responses, a chemical ligand of Vγ9Vδ2 T cells was used to enhance both proliferation and cytotoxic activity of anti-B lymphoma effectors. We show that such synthetic compound improves Vγ9Vδ2 CTL numbers and lysis of B lymphoma lines, especially when the targets are already spontaneously recognized by these effectors. We report here that human Vγ9Vδ2 T cells anti-B lymphoma response can be improved by use of specific synthetic ligands, which enhance their cytotoxic activity and allows their rapid expansion ex vivo.